Reviews in Analytical Chemistry 2021; 40: 75–92 Review Article Open Access Fugang Xu*, Mengren Xuan, Zixiang Ben, Wenjuan Shang, and Guangran Ma* Surface enhanced Raman scattering analysis with filter-based enhancement substrates: A mini review https://doi.org/110.1515/revac-2021-0126 strate is introduced. After that, the preparation of filter- received December 08, 2020; accepted February 15, 2021 based substrate and the role of filter are summarized. Then, the application of filter involved SERS substrate in Abstract: Surface enhanced Raman is a powerful analyti- analysis is presented. Finally, the challenges and perspec- cal tool with high sensitivity and unique specificity and tive on this topic is discussed. promising applications in various branches of analytical chemistry. Despite the fabrication of ingenious enhance- Keywords: SERS, flexible substrate, food safety, environ- ment substrate used in laboratory research, the develop- ment monitoring, concentration, separation ment of simple, flexible, and cost-effective substrate is also great important for promoting the application of SERS in practical analysis. Recently, paper and filter membrane as support to fabricate flexible SERS substrates received 1 Introduction considerable attentions. Paper-based SERS substrate Surface-enhanced Raman spectroscopy (SERS) has become has been reviewed but no summary on filter-based SERS one of the most versatile and powerful analytical tech- substrate is available. Compared with paper, filter memb- niques due to its ultrahigh sensitivity (single molecule), rane has unique advantage in robust mechanics, diverse unique “fingerprint” specificity and non-destructive analy- component, and tunable pore size. These characteristics sis in molecule sensing [1]. These unique advantages make endow the filter-based substrates great advantages for SERS a promising tool in various branches of analytical practical SERS analysis including simple and low-cost science, such as environment monitoring, food analysis, substrate preparation, high efficiency in preconcent- surface analysis, disease diagnosis and so on [1-3]. It is well ration, separation and detection procedure. Therefore, known efficient enhancement SERS substrates play a vital filter-based substrates have shown great promise in SERS role in achieving these advanced applications. Up to now, analysis in environment monitoring, food safety with high a mass of substrates with different components, structures sensitivity and efficiency. As more and more work has and arrangements have been developed, and these studies been emerged, it is necessary to summarize the state of continue. Searching new materials (semiconductor [4], such a research topic. Here, the research on filter invol- graphene [5], metal organic framework [6], etc.) to achieve ved SERS analysis in the past eight years is summarized. Raman signal enhancement is always an important topic in A short introduction was presented to understand the SERS research, and several excellent Reviews on this topic background, and then the brief history of filter-based sub- have been published [7-9]. Although many advanced Au/Ag micro- nano-structures or their hybrid with other materials have been developed for SERS analysis, most of them are * Corresponding author: Fugang Xu, College of Chemistry and only prototype used in lab analysis. The fabrication of these Chemical Engineering and Analytical and Testing Center, Jiangxi Normal University, Nanchang 330022, China, substrates often requires sophisticated equipment or ela- email: [email protected] (ORCID: 0000-0002-4165-8437) borate skills, or high cost, which makes it hard to massive * Corresponding author: Guangran Ma, College of Chemistry and production, and thus not available for practical analysis. Chemical Engineering and Analytical and Testing Center, Jiangxi In addition to explore new component material, Normal University, Nanchang 330022, China, the development of flexible and easy-prepared subst- email: [email protected], tel: +86-791-88120861 Mengren Xuan, Zixiang Ben, Wenjuan Shang: College of Chemistry rate becomes a new trend in recent years on the demand and Chemical Engineering and Analytical and Testing Center, Jiangxi of practical analysis [10-12]. On this issue, paper- or Normal University, Nanchang 330022, China filter-based SERS substrate have received considerable Open Access. © 2021 Fugang Xu et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution 4.0 International License. 76 Fugang Xu et al. attentions. Gold or silver nanoparticles prepared by wet- silicon slide) are often used as SERS substrate to incu- chemical synthesis can adsorbed on or assembly on fle- bate with target molecules for SERS analysis [21]. Directly xible matrix to form the flexible substrate. This substrate using plasmonic particle suspension as substrate is has good mechanical resistance, display high efficiency in simple, but the resulted SERS signal is poor in reprodu- target capture and detection on uneven surface, and can be cibility. Therefore, Au/Ag assembly with order/periodic cut into the desired size and shape, easily integrated with arrangement are developed to improve the reproducibility other structures or devices. That is why flexible substrates of SERS signal [22]. Nevertheless, the design and prepara- are important for advancing the real-world application of tion of perfect Au/Ag assembly needs sophisticated skills. SERS technology. Currently, flexible SERS substrates are In addition, SERS analysis using both of these substrate mainly based on fiber paper [13], filter membrane [14], needs a long-time incubation with target to improve the flexible polymers [15], carbon nanotubes, and graphene signal intensity, which leads to low detection efficiency. materials [16]. Paper-based flexible SERS substrate have Considering these issues, a fast, simple method to prepare been widely reported, and their progress has been sum- a highly active SERS substrate for sensitive and reproduci- marized by several good reviews published in recent years ble analysis is of great demand. [10-12,17,18]. Compared with paper, filter is more versatile in component and structure, robust in mechanism, and more efficient for concentration by rapid and large-volume 2.1 Origin filtration [19]. In addition, filtration can be used to achieve the fast and uniform assembly of plasmonic particles on In 2012, Yu and White [19] developed the first filter-based the filter or other matrix. These merits provide a guaran- SERS substrate, which is simple but highly efficient and tee to obtain a highly sensitive and reproducible SERS fulfills all these requirements. They used syringe, Ag sol signal, which is important for practical quantitative ana- suspension and filter membrane to prepare the filter- lysis. Therefore, filter-based SERS substrate have been based substrate as presented in Figure 1. The preparation developed with great foresight and have attracted many is simple, economic, and fast. The subsequent detec- researchers into the field, which shows great promise in tion is also simple and highly efficient as the filtration environmental monitoring, food analysis, and so on [19]. can not only concentration analyte, but also reduce the At present, there is no review published on filter detection time (by avoiding long time incubation) and membrane-based substrates for SERS analysis, although improve the signal reproducibility (by assembly AgNPs nanofiber-based membrane for SERS analysis have been on filter under vacuum filtration). Thus, such substrate summarized in 2018 [20]. To better understand the origin shows great promise in practical trace chemical analy- and progress of filter-based SERS analysis, and further sis, and more and more work are published on this topic promote its research, we summarize the work on this topic from then on [23-33]. in the past ten years here. We hope that it will play a posi- tive role in promoting SERS to be a competitive tool in fast and accurate practical analysis. The main contents of the paper include: (1) origin and evolution of filter-based SERS substrates, (2) preparation of filter-based SERS substrates, (3) roles of filter in SERS analysis, (4) applications of fil- ter-based substrates in SERS analysis, (5) challenges and perspective. The application is further divided into: (I) inor- ganic analysis, (II) organic analysis, (III) biomolecule analy- sis, and (IV) others depending on the type of analytes. About 50 related work on filter-based SERS analysis are cited. 2 Origin and evolution of filter-based SERS substrates Figure 1: Schematic the pioneer work from Ian’s group on the Previously, Au or Ag NPs suspension or exquisite Au/Ag fabrication, enrichment and SERS detection of filter-based substrate nanoparticle assembly on hard matrix (such as glass or prepared by simple syringe filtering [19]. Surface enhanced Raman scattering analysis with filter-based enhancement substrates 77 2.2 Evolution particles are assembled onto filter by physical filtra- tion, no surface treatment of the filter is needed, and As the research continues, various filters were used to the shape and size of Au/Ag can be easily tuned. fabricate the active SERS substrate. The material of filter 2. Adsorb or in situ growth of Au/Ag nanoparticles onto changes from paper [19,23] to organic polymer [19], glass filter or other matrix [34,35]. These two approaches fiber [24], AAO [25], or even use composite material itself are widely employed to prepare paper-based